Use of virologic assays for detection of human immunodeficiency virus in clinical trials: recommendations of the AIDS Clinical Trials Group Virology Committee

Crumpacker, Clyde S.; D’Aquila, Richard T.; Jackson, Brooks; Lathey, Janet L.; Livnat, Daniella; Reichelderfer, Patricia

doi:10.1128/jcm.31.10.2557-2564.1993

Cited by 60 publications

(25 citation statements)

References 47 publications

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“…A high degree of variability in the degree of stimulation was also observed. We do not feel this relates to the variability of the test used for the measurement of viral replication, which is, in itself, quite reliable and widely used (16). Rather, the variability may be linked to the different susceptibilities of the cells to HIV infection and/or to the effects of y-radiation.…”

Section: Discussionmentioning

confidence: 96%

Effect of Low‐Dose Gamma Radiation on HIV Replication in Human Peripheral Blood Mononuclear Cells

Conway

Montaner

et al. 1996

Photochem & Photobiology

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Recent studies have demonstrated that UV light and x-irradiation enhance human immunodeficiency virus (HIV) gene expression. There are few published data on related effects of gamma-radiation. This may be of clinical relevance, as radiotherapy has been used extensively for the treatment of acquired immunodeficiency syndrome associated conditions. With this in mind, we have studied the effects of gamma-radiation on HIV replication in mononuclear cells (MC). These cells were obtained from five seronegative healthy donors, exposed to 0-200 cGy gamma-radiation, stimulated with phytohemagglutinin-P (PHA-P) for 24 h, infected with a laboratory strain of HIV (HTLV-IIIB, multiplicity of infection = 0.001), then carried in culture for 14 days. Overall, when considering p24 antigen levels on days 7 and 11 in cultures established from cells exposed to 50 cGy, the maximal levels were significantly higher than those measured in the parallel control cultures taken as a whole (P < 0.05), with viral replication enhanced as much as 1000-fold in one case. No significant cytotoxicity was observed following exposure to doses up to 50 cGy. The mechanism of the observed effect remains unknown but may relate to direct gene activation and/or free radical generation, leading to such activation. To date, there is no evidence that viral stimulation occurs following therapeutic radiation in a clinical setting.

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Section: Discussionmentioning

confidence: 96%

Effect of Low‐Dose Gamma Radiation on HIV Replication in Human Peripheral Blood Mononuclear Cells

Conway

Montaner

et al. 1996

Photochem & Photobiology

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“…Inappropriate timing of specimens can result in the indicators of early HIV infection, such as seroconversion, a rise in antibody titre, p24 antigenaemia, and specific IgM [1][2][3], being missed. Furthermore, although indicative of early infection, p24 antigenaemia may reappear in the later stages of the disease [4] and HIV-specific IgM detection can be problematical [5].…”

Section: Introductionmentioning

confidence: 99%

Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1

Thomas

Wilson²,

O’Toole

et al. 1996

Clinical and Experimental Immunology

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SUMMARYWe have evaluated solid-phase ELISA IgG antibody avidity studies as a means of identifying cases of recent HIV-1 infection. Although separate studies on the avidity of anti-gp41 and anti-p24 antibodies in seroconvertors have been reported, a comparison of the ability of patients to simultaneously mature their immune response to more than one HIV antigen immediately following seroconversion appears to be lacking. We have demonstrated a maturation in anti-gp41 avidity which reflects the time since seroconversion in all cases. In contrast, however, only some patients produced high-avidity anti-p24 or anti-p17 antibodies during the same time span. While the avidity of anti-gp41 antibodies remained high in cases of non-recent HIV infection, even in the face of advanced disease, we have confirmed the findings of others that the avidity of anti-p24 falls before the onset of ARC or AIDS. Therefore, whilst the avidity of anti-gp41 antibodies could reliably be of value in identifying cases of recent HIV infection, the avidity of anti-p24 or anti-p17 antibodies could not, but may be of prognostic value, even at an early stage. The time taken to reach maximum anti-p17, anti-p24 and anti-gp41 titres was variable, but anti-gp41 titres, like anti-gp41 avidity, remained high. In contrast, anti-p24 titres fell, even during the early follow-up period in some seroconvertors. Anti-p24 antibody avidity, however, appeared to be a better predictor of disease progression in 'remote' cases than anti-p24 titre. The avidity and titres of these antibodies are presented in relation to the clinical details, p24 antigen status, CD4 and CD8 counts where these are known.Keywords anti-gp41 anti-p17 anti-p24 relative antibody avidity recent infection antibody titre

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“…Patients with CD4 ϩ counts of under 200/mm 3 and/or patients who have been diagnosed as having AIDS or AIDS-related complex show a higher p24 antigen prevalence rate (3,12). HIV antigen quantitation is useful as an easily measurable marker whose decline indicates the in vivo antiviral activities of anti-HIV agents and is helpful in the early evaluation of new agents (7). A decline in p24 antigen levels under antiretroviral therapy is associated with a corresponding increase in CD4 ϩ cells.…”

mentioning

confidence: 99%

“…The percentage of p24 antigenpositive patients increases with every subsequent stage of HIV disease after immune complex dissociation. Furthermore, sera that contain detectable levels of p24 antigen in the standard assay frequently yield higher concentrations after acid treatment (7).…”

mentioning

confidence: 99%

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Quantitative detection of human immunodeficiency virus (HIV) antigen by the Enzymun-Test: comparison with alternative assays and nucleic acid sequence-based amplification of HIV type 1 RNA

et al. 1996

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A new modular automated enzyme immunoassay (EIA) (Enzymun-Test HIV Ag; Boehringer Mannheim) for quantitative human immunodeficiency virus (HIV) antigen detection was evaluated by testing a panel of 1,506 serum samples, including seroconversions, dilution series, follow-up samples from patients under antiretroviral therapy, single serum specimens from HIV-seropositive individuals in different stages of infection, potentially cross-reactive samples, and sera from HIV-negative hospitalized patients. The Abbott HIV type 1 (HIV-1) antigen monoclonal antibody assay served as the reference assay, and nucleic acid sequence-based amplification (Organon Teknika) for quantitative amplification of HIV-1 RNA was used for follow-up of patients under antiretroviral chemotherapy. The Boehringer Mannheim and Abbott EIAs showed concordant results for the early detection of HIV antigen in all the seroconversion panels. The follow-up samples from 29 HIV-infected individuals under antiretroviral therapy gave divergent results between both antigen tests. For the detection of HIV antigen in single serum samples from HIV-infected patients in different stages of HIV infection, a higher number of positive samples was detected with the Abbott HIV-1 antigen monoclonal antibody assay in samples from patients in stages II and III of HIV infection. TheEnzymun-Test detected three more positive samples than did the Abbott assay among the samples of patients with AIDS. The concordance on a sample-to-sample basis between the Boehringer Mannheim and Abbott EIAs was 98.6%. The sensitivity of the Enzymun-Test in comparison to the reference assay was 97.2%; the specificity was 98.8%. Although no close correlation could be found between the amount of viral RNA in serum detected by nucleic acid sequence-based amplification and the concentration of HIV antigen, a high HIV-1 RNA copy number was mostly associated with high levels of HIV antigen. In conclusion, the Enzymun-Test permits accurate HIV antigen detection and offers, in contrast to previous assays, the possibility of completely automated detection.

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Use of virologic assays for detection of human immunodeficiency virus in clinical trials: recommendations of the AIDS Clinical Trials Group Virology Committee

Cited by 60 publications

References 47 publications

Effect of Low‐Dose Gamma Radiation on HIV Replication in Human Peripheral Blood Mononuclear Cells

Effect of Low‐Dose Gamma Radiation on HIV Replication in Human Peripheral Blood Mononuclear Cells

Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1

Quantitative detection of human immunodeficiency virus (HIV) antigen by the Enzymun-Test: comparison with alternative assays and nucleic acid sequence-based amplification of HIV type 1 RNA

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